Abstract
Deregulation of transforming growth factor-Β (TGFΒ) signaling has been reported in human psoriasis. Our recent study using a keratin 5 promoter (K5.TGFΒ1 wt) showed that transgenic mice expressing wild-type TGFΒ1 in the epidermis developed severe skin inflammation. Additional experimental data further support a direct role for TGFΒ1 overexpression in skin inflammation. First, we temporally induced TGFΒ1 expression in keratinocytes in our gene-switch TGFΒ1 wt transgenic mice and found inflammation severity correlated with TGFΒ1 wt transgene expression. Second, deletion of T cells in K5.TGFΒ1 wt mice significantly delayed skin inflammation and associated epidermal hyperplasia/hyperkeratosis. Third, therapeutic approaches effective for human psoriasis, that is, Etanercept and Rosiglitazone, are effective in alleviating the symptoms observed in K5.TGFΒ1 wt mice. Future studies will analyze specific mechanisms and identify key factors in TGFΒ1-induced skin inflammation. Our mouse models will provide a useful tool for understanding the molecular mechanisms of inflammatory skin disorders in which TGFΒ1 is overexpressed. © 2010 The Society for Investigative Dermatology.